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乙酰胆碱的体内剂量反应分析:偏振反射光谱法的药效学评估。

In vivo dose-response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy.

机构信息

Department of Emergency Medicine, Local Health Care Services in Central Östergötland, 58182, Linköping, Sweden.

Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

出版信息

Sci Rep. 2022 Apr 21;12(1):6594. doi: 10.1038/s41598-022-10617-x.

DOI:10.1038/s41598-022-10617-x
PMID:35449189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9023454/
Abstract

Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose-response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.

摘要

经皮离子电渗疗法为血管功能的测量提供了一种体内替代应变计模型的方法,但由于缺乏用于结果评估的技术解决方案而受到限制。本研究的目的是在偏振反射光谱(PRS)测量后,使用对不同浓度乙酰胆碱(ACh)的反应的药效剂量反应分析;并检查连续三次给予离子电渗电流脉冲的效果。使用 PRS 记录了 15 名健康志愿者对离子电渗 ACh(5 种浓度,范围为 0.0001%至 1%,每个脉冲 0.02 mA 持续 10 分钟,连续三个脉冲)的血管反应。数据拟合到四参数逻辑剂量反应模型并进行比较。PRS 可定量评估血管反应。无论 ACh 浓度如何,均可产生相似的药效剂量反应曲线。随着 ACh 浓度的增加,最大血管舒张反应呈线性增加。在脉冲之间观察到 ACh 浓度的线性剂量效应有限。偏振反射光谱非常适合测量经离子电渗给药的 ACh 引起的血管反应。本研究的结果支持进一步开发离子电渗作为研究体内血管功能和药理反应的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/a87062166ae9/41598_2022_10617_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/86124bb265e1/41598_2022_10617_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/a9c0c8574881/41598_2022_10617_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/f56c5f5336a2/41598_2022_10617_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/c2870ef088d8/41598_2022_10617_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/a87062166ae9/41598_2022_10617_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/86124bb265e1/41598_2022_10617_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/a9c0c8574881/41598_2022_10617_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/f56c5f5336a2/41598_2022_10617_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/c2870ef088d8/41598_2022_10617_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0a/9023454/a87062166ae9/41598_2022_10617_Fig5_HTML.jpg

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本文引用的文献

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